Jul 6, 2014

β-amyloid deposition is shifted to the vasculature and memory impairment is exacerbated when hyperhomocysteinemia is induced in APP/PS1 transgenic mice

Alzheimer's Research & Therapy
Tiffany L SudduthDonna M Wilcock

Abstract

Vascular dementia is the second most common cause of dementia after Alzheimer's disease (AD). In addition, it is estimated that almost half of all AD patients have significant cerebrovascular disease comorbid with their AD pathology. We hypothesized that cerebrovascular disease significantly impacts AD pathological progression. We used a dietary model of cerebrovascular disease that relies on the induction of hyperhomocysteinemia (HHcy). HHcy is a significant clinical risk factor for stroke, cardiovascular disease and type 2 diabetes. In the present study, we induced HHcy in APP/PS1 transgenic mice. While total β-amyloid (Aβ) load is unchanged across groups, Congophilic amyloid deposition was decreased in the parenchyma and significantly increased in the vasculature as cerebral amyloid angiopathy (CAA; vascular amyloid deposition) in HHcy APP/PS1 mice. We also found that HHcy induced more microhemorrhages in the APP/PS1 mice than in the wild-type mice and that it switched the neuroinflammatory phenotype from an M2a biased state to an M1 biased state. Associated with these changes was an induction of the matrix metalloproteinase protein 2 (MMP2) and MMP9 systems. Interestingly, after 6 months of HHcy, the APP/PS1 mice were cogni...Continue Reading

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Mentioned in this Paper

Diabetes Mellitus, Non-Insulin-Dependent
Parenchyma
APP protein, human
Cerebral Amyloid Angiopathy
Matrix Metalloproteinase 2 Measurement
Blood Vessel
Brain
Matrix Metalloproteinase 2
Plaque, Amyloid
Homocysteinemia

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